Aim 1: Develop and Implement High-Throughput Kinase Assays for Monitoring the Signaling Response to DNA Damage. Aim 2: Monitor Kinase Localization, Cell Cycle Progression, and Apoptosis in Response to DNA Damage. Aim 3: Construct a Quantitative Predictive Systems Biology Model for Protein Kinase Network Responses During DNA Damage Signaling. Aim 4. Utilize Knock-Out Mutant Analysis, shRNA Technologies, and Genetic Engineering in Cells and Mice to Test Hypotheses Generated from the Model and to Further Probe DNA Damage Signaling Networks. Aim 5 - Discovery of New Kinase Substrates that Play Key Roles in the DNA Damage Response.